A Narrative Review of Patient-Reported Outcome Measures and Their Application in Recent Pediatric Surgical Research: Advancing Knowledge and Offering New Perspectives to the Field.

INTRODUCTION: Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research. MATERIALS AND METHODS: A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described. RESULTS: Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study. CONCLUSIONS: This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies.

Development and validation of a condition-specific quality of life instrument for adults with esophageal atresia: the SQEA questionnaire.

The importance of multidisciplinary long-term follow-up for adults born with esophageal atresia (EA) is increasingly recognized. Hence, a valid, condition-specific instrument to measure health-related quality of life (HRQoL) becomes imperative. This study aimed to develop and validate such an instrument for adults with EA. The Specific Quality of life in Esophageal atresia Adults (SQEA) questionnaire was developed through focus group-based item generation, pilot testing, item reduction and a multicenter, nationwide field test to evaluate the feasibility, reliability (internal and retest) and validity (structural, construct, criterion and convergent), in compliance with the consensus-based standards for the selection of health measurement instruments guidelines. After pilot testing (n = 42), items were reduced from 144 to 36 questions. After field testing (n = 447), three items were discarded based on item-response theory results. The final SQEA questionnaire (33 items) forms a unidimensional scale generating an unweighted total score. Feasibility, internal reliability (Cronbach's alpha 0.94) and test-retest agreement (intra-class coefficient 0.92) were good. Construct validity was discriminative for esophageal replacement (P < 0.001), dysphagia (P < 0.001) and airway obstruction (P = 0.029). Criterion validity showed a good correlation with dysphagia (area under the receiver operating characteristic 0.736). SQEA scores correlated well with other validated disease-specific HRQoL scales such as the GIQLI and SGRQ, but poorly with the more generic RAND-36. Overall, this first condition-specific instrument for EA adults showed satisfactory feasibility, reliability and validity. Additionally, it shows discriminative ability to detect disease burden. Therefore, the SQEA questionnaire is both a valid instrument to assess the HRQoL in EA adults and an interesting signaling tool, enabling clinicians to recognize more severely affected patients.

Psychometric Performance of the Stony Brook Scar Evaluation Scale and SCAR-Q Questionnaire in Dutch Children after Pediatric Surgery.

Introduction: The growing population of survivors following pediatric surgery emphasizes the importance of long-term follow-up. The impact of surgical scars on daily life can be evaluated through patient-reported outcome measurements. The Stony Brook Scar Evaluation Scale (SBSES) and SCAR-Q questionnaire are two interesting instruments for this purpose. We evaluated their psychometric performance in Dutch children after pediatric surgery. Methods: After English-Dutch translation, we evaluated-following the COSMIN guidelines-the feasibility, reliability (internal and external), and validity (construct, criterion, and convergent) of the SBSES and SCAR-Q in Dutch patients < 18 years old with surgical scars. Results: Three independent observers completed the SB for 100 children (58% boys, median age 7.3 (IQR 2.5-12.1) years) in whom surgery had been performed a median of 2.8 (0.5-7.9) years ago. Forty-six of these children (61% boys, median age 12.1 (9.3-16.2) years) completed the SCAR-Q. Feasibility and internal reliability (Cronbach's alpha > 0.7) was good for both instruments. For the SB, external reliability was poor to moderate (interobserver variability: ICC 0.46-0.56; intraobserver variability: ICC 0.74). For the SCAR-Q, external reliability was good (test-retest agreement: ICC 0.79-0.93). Validity tests (construct, criterion, and convergent) showed poor to moderate results for both instruments. Conclusions: The Dutch-translated SBSES and SCAR-Q showed good feasibility and internal reliability. External reliability and validity were likely affected by differences in conceptual content between the questionnaires. Combining them would provide insight in the impact of scars on patients. Implementation of these instruments in longitudinal follow-up programs could provide new insights into the long-term psychological outcome after pediatric surgery.

Psychometric Performance of a Condition-Specific Quality-of-Life Instrument for Dutch Children Born with Esophageal Atresia.

A condition-specific instrument (EA-QOL©) to assess quality of life of children born with esophageal atresia (EA) was developed in Sweden and Germany. Before implementing this in the Netherlands, we evaluated its psychometric performance in Dutch children. After Swedish−Dutch translation, cognitive debriefing was conducted with a subset of EA patients and their parents. Next, feasibility, reliability, and validity were evaluated in a nationwide field test. Cognitive debriefing confirmed the predefined concepts, although some questions were not generally applicable. Feasibility was poor to moderate. In 2-to-7-year-old children, 8/17 items had >5% missing values. In 8-to-17-year-old children, this concerned 3/24 items of the proxy-report and 5/14 items of the self-report. The internal reliability was good. The retest reliability showed good correlation. The comparison reliability between self-reports and proxy-reports was strong. The construct validity was discriminative. The convergent validity was strong for the 2-to-7-year-old proxy-report, and weak to moderate for the 8-to-17-year-old proxy-report and self-report. In conclusion, the Dutch-translated EA-QOL questionnaires showed good reliability and validity. Feasibility was likely affected by items not deemed applicable to an individual child's situation. Computer adaptive testing could be a potential solution to customizing the questionnaire to the individual patient. Furthermore, cross-cultural validation studies and implementation-evaluation studies in different countries are needed.

Intrinsic Cellular Susceptibility to Barrett's Esophagus in Adults Born with Esophageal Atresia.

The prevalence of Barrett's esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.

Recommendations for endoscopic surveillance after esophageal atresia repair in adults.

BACKGROUND: Endoscopic surveillance of adults with esophageal atresia is advocated, but the optimal surveillance strategy remains uncertain. This study aimed to provide recommendations on appropriate starting age and intervals of endoscopic surveillance in adults with esophageal atresia. METHODS: Participants underwent standardized upper endoscopies with biopsies. Surveillance intervals of 3-5 years were applied, depending on age and histopathological results. Patient's age and time to development of (pre)malignant lesions were calculated. RESULTS: A total of 271 patients with esophageal atresia (55% male; median age at baseline endoscopy 26.7 (range 15.6-68.5) years; colon interposition n = 17) were included. Barrett's esophagus was found in 19 (7%) patients (median age 32.3 (17.8-56.0) years at diagnosis). Youngest patient with a clinically relevant Barrett's esophagus was 20.9 years. Follow-up endoscopies were performed in 108 patients (40%; median follow-up time 4.6 years). During surveillance, four patients developed Barrett's esophagus but no dysplasia or cancer was found. One 45-year-old woman with a colon interposition developed an adenoma with high-grade dysplasia which was radically removed. Two new cases of esophageal carcinoma were diagnosed in patients (55 and 66 years old) who were not under surveillance. One of them had been curatively treated for esophageal carcinoma 13 years ago. CONCLUSIONS: This study shows that endoscopic screening of patients with esophageal atresia, including those with a colon interposition, can be started at 20 years of age. Up to the age of 40 years a surveillance interval of 10 years appeared to be safe. Endoscopic surveillance may also be warranted for patients after curative esophageal cancer treatment.

Sex differences in children's health status as measured by the Pediatric Quality of Life Inventory (PedsQL)™: cross-sectional findings from a large school-based sample in the Netherlands.

BACKGROUND: Previous research has shown that female adolescents and adults report lower health status than their male peers. Possibly, this discrepancy already develops during childhood. We collected sex-specific data with the Pediatric Quality of Life Inventory (PedsQL) in a large school-based sample. METHODS: The online version of the PedsQL was administered to healthy Dutch children aged 5-7 years (parent proxy-report), 8-12 years (parent proxy-report and child self-report), and 13-17 years (parent proxy-report and child self-report), recruited through regular primary and secondary schools. Sex differences were assessed using t-tests or Mann-Whitney U-tests. Wilcoxon signed-rank tests and intraclass correlation coefficients served to compare parent proxy-reports with child self-reports. Multivariable linear regression analyses were used to assess the associations of sex of the child, age, and parental educational level with PedsQL scores. RESULTS: Eight hundred eighty-two parents and five hundred eighty one children were recruited from 15 different schools in the Netherlands. Parents of 8-to-12-year-olds reported higher scores on School Functioning for girls than for boys (mean difference [MD]: 6.56, p < 0.001). Parents of 13-to-17-year-olds reported lower scores on Physical and Emotional Functioning for girls than for boys (MDs: 2.14 and 5.79, p = 0.014 and p < 0.001, respectively). Girls aged 8-12 years reported lower scores than boys in this age group on Physical Functioning (MD: 3.09, p = 0.005). Girls aged 13-17 years reported lower scores than boys in this age group on Physical Functioning (MD: 3.67, p < 0.001), Emotional Functioning (MD: 8.11, p < 0.001), and the Total Score (MD 3.26, p = 0.004). No sex differences were found in children aged 5-7 years. Agreement between child self-reports and parent proxy-reports was poor to moderate. CONCLUSIONS: Girls generally had lower PedsQL scores than boys, both in parent proxy-reports and in child self-reports. We recommend to apply sex-specific data when assessing health status using the PedsQL.

Longitudinal Health Status and Quality of Life After Esophageal Atresia Repair.

OBJECTIVES: To longitudinally evaluate self-reported and proxy-reported health status (HS) and quality of life (QoL) of school-aged children born with esophageal atresia (EA). METHODS: We obtained Pediatric Quality of Life Inventory (HS) and DUX-25 (QoL) questionnaires from children born with EA between 1999 and 2011 at 8 and/or 12 years old. Children completed self-reports during neuropsychological assessments in a prospective longitudinal follow-up program. Parents filled out proxy-reports at home. Total and subscale scores were evaluated longitudinally and compared with sex-specific reference norms. RESULTS: In total, 110 participants (62% boys) were included. Self-reported HS improved significantly between 8 and 12 years for both boys (mean difference [md] 4.35, effect size [ES] 0.54, P = 0.009) and girls (md 3.26, ES 0.63, P = 0.004). Proxy-reported HS tended to improve over time, while self-reported and proxy-reported QoL tended to decline. Self-reported HS at 8 years was below normal for both boys (md -5.44, ES -0.35, P < 0.001) and girls (md -7.61, ES -0.32, P < 0.001). Girls' self-reported QoL was below normal at 8 (md -5.00, ES -0.18, P = 0.019) and 12 years (md -10.50, ES -0.26, P = 0.001). Parents reported normal HS at both ages, whereas they rated the QoL of their daughters below normal at 12 years (md -10.00, ES -0.16, P = 0.022). All above results are total scores. CONCLUSIONS: Self-reported and proxy-reported HS of children with EA improved between 8 and 12 years, while their QoL tended to decline. We recommend to consider HS and QoL as two separate concepts and to measure both simultaneously and longitudinally when evaluating the burden of disease.

Patient-Reported Outcome Measures and Clinical Outcomes in Children with Foregut Anomalies.

Increasing numbers of children and adults with chronic disease status highlight the need for a value-based healthcare system. Patient-reported outcome measures (PROMs) are essential to value-based healthcare, yet it remains unclear how they relate to clinical outcomes such as health and daily functioning. We aimed to assess the added value of self-reported PROMs for health status (HS) and quality of life (QoL) in the long-term follow-up of children with foregut anomalies. We evaluated data of PROMs for HS and/or QoL among eight-year-olds born with congenital diaphragmatic hernia (CDH), esophageal atresia (EA), or congenital lung malformations (CLM), collected within the infrastructure of a multidisciplinary, longitudinal follow-up program. Clinical outcomes were categorized into different outcome domains, and their relationships with self-reported HS and QoL were assessed through multivariable linear regression analyses. A total of 220 children completed HS and/or QoL self-reports. In children with CDH and EA, lower cognition was significantly associated with lower self-reported HS. Due to the low number of cases, multivariable linear regression analysis was not possible in children with CLM. HS, QoL, and clinical outcomes represent different aspects of a child's wellbeing and should be measured simultaneously to facilitate a more holistic approach to clinical decision making.

Long-term neurodevelopment in children born with esophageal atresia: a systematic review.

BACKGROUND: Although the survival rate of esophageal atresia (EA) has increased to over 90%, the risk of functional long-term neurodevelopmental deficits is uncertain. Studies on long-term outcomes of children with EA show conflicting results. Therefore, we provide an overview of the current knowledge on the long-term neurodevelopmental outcome of children with EA. METHODS: We performed a structured literature search in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google scholar on November 8, 2020 with the keywords 'esophageal atresia', 'long-term outcome', 'motor development', 'cognitive development', and 'neurodevelopment'. RESULTS: The initial search identified 945 studies, of which 15 were included. Five of these published outcomes of multiple tests or tested at multiple ages. Regarding infants, one of six studies found impaired neurodevelopment at 1 year of age. Regarding preschoolers, two of five studies found impaired neurodevelopment; the one study assessing cognitive development found normal cognitive outcome. Both studies on motor function reported impairment. Regarding school-agers, the one study on neurodevelopmental outcome reported impairment. Cognitive impairment was found in two out of four studies, and motor function was impaired in both studies studying motor function. CONCLUSIONS: Long-term neurodevelopment of children born with EA has been assessed with various instruments, with contrasting results. Impairments were mostly found in motor function, but also in cognitive performance. Generally, the long-term outcome of these children is reason for concern. Structured, multidisciplinary long-term follow-up programs for children born with EA would allow to timely detect neurodevelopmental impairments and to intervene, if necessary.

Patient-driven healthcare recommendations for adults with esophageal atresia and their families.

BACKGROUND: Adults with esophageal atresia (EA) require a multidisciplinary follow-up approach, taking into account gastroesophageal problems, respiratory problems and psychosocial wellbeing. Too little is known about the full scope of these individuals' healthcare needs. We aimed to map all medical and psychosocial needs of adults with EA and their family members, and to formulate healthcare recommendations for daily practice. METHODS: A qualitative study was performed, using data from recorded semi-structured interviews with two focus groups, one consisting of adult patients with EA (n = 15) and one of their family members (n = 13). After verbatim transcription and computerized thematic analysis, results were organized according to the International Classification of Functioning, Disability and Health. Ethical approval had been obtained. RESULTS: Healthcare needs were described through 74 codes, classified into 20 themes. Most important findings for patients included the impact of gastrointestinal and pulmonary problems on daily life, long-term emotional distress of patients and parents and the need of a standardized multidisciplinary follow-up program during both child- and adulthood. CONCLUSION: The focus groups revealed numerous physical and mental health problems, as well as social difficulties, that require attention from different healthcare providers. We have formulated several healthcare recommendations that physicians may use in long-term follow-up.

An international survey on anastomotic stricture management after esophageal atresia repair: considerations and advisory statements.

BACKGROUND: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor's experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. METHODS: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. RESULTS: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5-300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. CONCLUSIONS: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

Infantile hypertrophic pyloric stenosis in patients with esophageal atresia.

BACKGROUND: Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. METHODS: We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array-based genotyping, and compared the results to mouse transcriptome data of the developing foregut. RESULTS: We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10-5 ): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells. CONCLUSIONS: None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated.

The effect of intralesional steroid injections on esophageal strictures and the child as whole: A case series.

BACKGROUND: The most frequent complication after esophageal atresia repair remains anastomotic stricture formation. The initial treatment is endoscopic dilatation. Intralesional steroid injection (ISI) might be an effective adjuvant treatment in case of recurrent strictures. In this series we present our initial experience with this intervention. METHODS: Data on primary surgery, stricture treatment, postoperative complications, outcome and growth were retrospectively collected from electronic patient records. Findings were analyzed by descriptive statistics and mixed model analysis. RESULTS: Between 2014 and 2017, ISI was performed for severe recurrent anastomotic strictures in six patients (median age at injection 12.4 (2.1-34.7) months) after a median of 6 (2-20) dilatations. In five patients ISI was successful and the stenosis was cleared. No postoperative complications were reported, especially none related to acute adrenal suppression. Comparing the year before with the year after ISI, a significant positive change for weight (r = 0.70, p = 0.003) was calculated versus a negative change for height (r = -0.87, p = 0.003). CONCLUSIONS: We found ISI to be an effective adjuvant treatment to recurrent anastomotic stricture dilatation after esophageal atresia repair, without postoperative complications or symptoms of adrenal suppression. It remains important, however, to monitor growth effects. Further evaluation is required in a large prospective study. TYPE OF STUDY: Treatment study, Level IV (case series).

Intralesional steroid injections to prevent refractory strictures in patients with oesophageal atresia: study protocol for an international, multicentre randomised controlled trial (STEPS-EA trial).

INTRODUCTION: Anastomotic stricture formation is the most common postoperative complication after oesophageal atresia (OA) repair. The standard of care is endoscopic dilatation. A possible adjuvant treatment is intralesional steroid injection, which is thought to inhibit scar tissue formation and thereby to prevent stricture recurrence. We hypothesise that this intervention could prevent refractory strictures and reduce the total number of dilatations needed in these children. METHODS AND ANALYSIS: This is an international multicentre randomised controlled trial. Children with OA type C (n=110) will be randomised into intralesional steroid injection followed by balloon dilatation or dilatation only. Randomisation and intervention will take place when a third dilatation is performed. The indication for dilatation will be confirmed with an oesophagram. One radiologist-blinded for randomisation-will review all oesophagrams. The primary outcome parameter is the total number of dilatations needed with <28 days' interval, which will be analysed with a linear-by-linear χ2 association test. Secondary outcome parameters include the level of dysphagia, the luminal oesophageal diameter and stricture length (measured on the oesophagrams), the influence of comedication on stricture formation, systemic effects of intralesional steroids (cortisol levels, length and weight) and the cost-effectiveness. Patients will undergo a second oesophagram; length and weight will be measured repeatedly; a scalp hair sample will be collected; and three questionnaires will be administered. The follow-up period will be 6 months, with evaluation at 2-3 weeks, 3 and 6 months after the intervention. ETHICS AND DISSEMINATION: Patients will be included after written parental informed consent. The risks and burden associated with this trial are minimal. The institutional review board of the Erasmus Medical Centre approved this protocol (MEC-2018-1586/NL65364.078.18). The results of the trial will be published in a peer-reviewed scientific journal and will be presented at international conferences. TRIAL REGISTRATION NUMBERS: 2018-002863-24 and NTR7726/NL7484.

Developing social marketed individual preconception care consultations: Which consumer preferences should it meet?

AIMS: Preconception care (PCC) is care that aims to improve the health of offspring by addressing risk factors in the pre-pregnancy period. Consultations are recognized as a method to promote perinatal health. However, prospective parents underutilize PCC services. Uptake can improve if delivery approaches satisfy consumer preferences. Aim of this study was to identify preferences of women (consumers) as a first step to social marketed individual PCC consultations. METHODS: In depth, semi-structured interviews were performed to identify women's views regarding the four components of the social marketing model: product (individual PCC consultation), place (setting), promotion (how women are made aware of the product) and price (costs). Participants were recruited from general practices and a midwife's practice. Content analysis was performed by systematic coding with NVIVO software. RESULTS: The 39 participants reflected a multiethnic intermediately educated population. Product: Many participants had little knowledge of the need and the benefits of the product. Regarding the content of PCC, they wish to address fertility concerns and social aspects of parenthood. PCC was seen as an informing and coaching service with a predominant role for health-care professionals. PLACE: the general practitioner and midwife setting was the most mentioned setting. Promotion: A professional led promotion approach was preferred. Price: Introduction of a fee for PCC consultations will make people reconsider their need for a consultation and could exclude vulnerable patients from utilization. CONCLUSION: This study provides consumer orientated data to design a social marketed delivery approach for individual PCC consultations.

Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience.

BACKGROUND: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands. RESULTS: In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare. CONCLUSION: An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Diagnostic study.

High-Sensitivity Troponin T and N-Terminal Pro-Brain Natriuretic Peptide in Prediction of Outcome in Congenital Diaphragmatic Hernia: Results from a Multicenter, Randomized Controlled Trial.

UNLABELLED: Biomarkers may be helpful in prediction of outcomes of infants with congenital diaphragmatic hernia. The predictive value of high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide was investigated in 128 infants with congenital diaphragmatic hernia. After correction for multiple testing, those biomarkers did not predict severe pulmonary hypertension, death, need of extracorporeal membrane oxygenation, or bronchopulmonary dysplasia. TRIAL REGISTRATION: Netherlands Trial Registry: 1310.

B-type natriuretic peptide as a parameter for pulmonary hypertension in children. A systematic review.

UNLABELLED: Pulmonary hypertension (PH) is a life-threatening disease with a high mortality rate and a broad variety of underlying etiologies. The current golden standard for diagnosing PH and monitoring efficiency of treatment is right heart catheterization. As an alternative, serum biomarkers have been suggested. Cardiac troponin T (TnT), brain natriuretic peptide (BNP), and NT-proBNP seem the most potential. The aim of this systematic review was to evaluate the current literature on the prognostic value of these biomarkers in children with PH and their usefulness as a diagnostic tool. A systematic literature search yielded 14 studies on patients ≤18 years with proven PH with (NT-pro)BNP or TnT as primary outcome. TnT is suggested to be a promising biomarker, but its usefulness in clinical practice has not been proven. The levels of (NT-pro)BNP seemed to be reliable within one PH category, but differed significantly between categories. NT-proBNP showed a good correlation with mortality and might have a prognostic value. CONCLUSION: The lack of absolute levels makes (NT-pro)BNP unsuitable as a diagnostic marker, but in view of the relative changes, it could be used to monitor patients. Further investigation should explore differences in normal (NT-pro)BNP levels between the different categories of PH. WHAT IS KNOWN: • Pulmonary hypertension is a life-threatening disease. Diagnosis can be challenging in children; the current diagnostic options-right heart catheterization and echocardiography-are invasive and/or investigator-dependent procedures. • Biomarkers could be useful in this context because they are investigator independent and easy to obtain through blood samples. Brain natriuretic peptide (BNP) and its N-terminal cleavage product (NT-proBNP) seem to be the most promising. The value of these biomarkers in the diagnostic approach of PH has already been investigated in adults, with promising results. Pediatric studies are still scarce. What is new: • The levels of BNP and NT-proBNP in pediatric patients differ strongly between the different categories of PH. Within the same category, the levels are more or less equal. • The relative changes could render them a prognostic marker in the follow-up of a certain individual patient. At this moment there is not enough evidence to rely on BNP or NT-proBNP in clinical treatment of patients with PH.

[Prevention of injuries associated with horseback riding]. / Preventie van letsels in de paardensport.

Each year 9,900 equestrians present at Accident and Emergency Departments, 40% of them 10-19 year old females. The most common horse-riding injuries are to the head, brain, neck and face, torso and extremities. Because of the relatively larger head, children more often fall on their head. Wearing a helmet gives considerable protection. Despite the common use of a helmet by horseback riders, serious head injury still occurs regularly. Further research into improvement of the protective function of the helmet is indicated. The current safety vest (body protector) does not significantly reduce the risk of torso injury. Improvement of its protective function is necessary. Injury to the lower extremities is caused when they become trapped in the stirrup in a fall from or with the horse. Safety stirrups and sturdy footwear are possible preventive measures. Investment in the quality and promotion of preventive measures could reduce the frequency and severity of equestrian injuries.